Aquaculture is the fastest growing animal food production sector globally. Fish are an import source of protein and as such aquaculture has great potential to play a key role in future food security programmes. Because of their rapid growth and high protein content, tilapia is an attractive species for aquaculture, reaching harvest size after only 6-7 months; tilapia are now in fact the second most farmed species after carp. They are farmed in many low and middle-income countries (LMIC) and provide an important source of revenue for many low income families. Disease in tilapia culture is associated with intensification of the farming system, and both bacterial and viral diseases are severely impacting on the expansion of tilapia farming; in particular Streptococcus spp. There is increasing concern about the use of antibiotics to control disease outbreaks and attention is focusing on the use of vaccination for disease control. Vaccination exposes fish to a non-infectious dose of the pathogen, so when they come into contact with the pathogen at a later date, memory cells of their immune system stimulate a response to combat the disease. We need a better understanding of how tilapia respond to infection and vaccination to be able to develop and formulate effective vaccine products for tilapia. We currently have few reagents available for investigating the immune response of tilapia. Through a collaboration of scientists in Vietnam, Canada and the UK, we plan to develop and apply novel tools (synthetic antibodies) for studying the immune response of this important aquaculture species, using Streptococcus agalactiae as our infection model. Synthetic antibodies are made in the laboratory, unlike conventional antibodies which are produce in animals, thus eliminating the need to use animals to make these reagents. This work will ultimately lead to the development of more effective strategies for managing disease in tilapia aquaculture systems.

Low-cost thermostabilisation of a Rift Valley Fever vaccine for veterinary use

Vaccines are among the most cost-effective public health interventions ever developed. However, many of the currently available products require refrigeration in order to maintain their viability and ability to elicit a protective immune response in humans or animals. This requirement for a ‘cold chain’ has major cost implications, and remains a major challenge in the deployment of vaccines in resource-poor settings where uninterrupted supply of electricity to maintain a cold chain in fridges is unavailable. In this project we aim to develop and optimise a low-cost method of formulating vaccines to obviate the need for refrigeration. We will exploit the known properties of certain sugars, trehalose and sucrose, to thermostabilise live viruses when slowly desiccated on to fibrous membranes with minimal loss in viability. We will adapt an existing method to make it suitable for stabilisation of very low cost veterinary vaccine formulations, which are not purified to the same extent as human formulations. To demonstrate the utility of this new method, we will thermostabilise an advanced candidate vaccine in development for Rift Valley Fever (ChAdOx1 RVF) in humans and animals, and evaluate its viability and ability to elicit an immune response in mice following storage at low (4C), medium (20C) and high (45C) temperatures for 6 months. If successful, the thermostable ChAdOx1 RVF will be further developed for commercialisation, both for the human and veterinary indications. The data generated in this project will also be useful in informing thermostabilisation protocols for other veterinary (and human) vaccines.

Taenia solium is the aetiological agent of neurocysticercosis in humans and is associated with a high frequency of epilepsy in endemic areas. Pigs are the almost exclusive natural animal intermediate host for T. solium and immunisation of pigs offers the opportunity for disease prevention. Despite the general difficulty of effective immunisation against complex parasites Lightowlers in Melbourne has developed a highly effective protein in adjuvant vaccine based on the TSOL18 antigen. Two doses of this vaccine lead to very high level protection of >98% in pigs in a variety of rural disease settings where the vaccine is most needed. However, deployment of two doses of vaccine in pigs in such settings is proving highly logistically problematic and a single dose of this vaccine has been found to be insufficiently protective. We propose here to assess for the first time the potential of a viral vectored adenovirus vaccine encoding the same TSOL18 antigen. Adenoviral vectors are known to provide excellent antibody responses with a single dose in a range of animal species, including pigs, and in humans, as illustrated by their use as a single dose vaccine in the Ebola rapid response vaccine programme in 2014. We propose to make adenoviral vectors for this Taenia antigen, test immune responses in mice initially and then critically in pigs. By comparing the immune response generated in pigs by a single dose of the new adenoviral vaccine to that generated by two doses of the existing protein in adjuvant vaccine, we will be able to determine whether a single dose adenoviral vaccine is a viable option for further development as a single dose vaccine for prevention of Taenia solium disease.

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